Analysis of a biologically active molecular clone of simian sarcoma virus (SSV) has shown that the 5.1 kbp genome contains a 1.0 kbp segment (v-sis) which is derived from a unique woolly monkey cellular gene. Utilizing SSV deletion mutants constructed in vitro, we have demonstrated that v-sis is required for the induction and maintenance of transformation. Analysis of the primary nucleotide sequence of v-sis has revealed a 675 bp open reading frame commencing 19 nucleotides upstream of the v-sis helper virus junction and terminating within v-sis. This open reading frame has the capacity to code for a 28,000 dalton protein. A small peptide selected from the amino acid sequence of the predicted v-sis gene product was used as an immunogen to prepare antiserum. The peptide antibody detected a v-sis coded protein of 28,000 daltons (p28sis) expressed specifically in SSV transformed cells. Preliminary characterization of p28sis indicates that properties of this onc gene product differ from those of other described retrovirus transforming proteins. Other studies have described the chromosomal localization of a gene analogous to v-sis within the human genome and have demonstrated activation of this gene in certain types of human tumor cells.